APPLICANT'S ABSTRACT: The proposed research will delineate the subjective, cardiovascular and behavioral interaction between alcohol and nicotine. Moreover, a novel pharmacologic approach for smoking cessation and alcoholism treatment involving administration of nicotine and the nicotinic antagonist mecamylamine will be explored. In Study 1, the acute interactive effects of controlled doses of alcohol and cigarette smoke will be measured in the laboratory. Subjective and cardiovascular effects as well as indices of cognitive performance will be measured before and after different doses of alcohol are consumed and nicotine-containing vs de-nicotinized cigarettes are smoked. In Study 2, the interactions between alcohol and nicotine administered in skin patches will be assessed. Study 3 will investigate the role of nicotinic neurotransmission in alcohol reward by measuring the effects of controlled doses of alcohol following administration of the nicotinic antagonist mecamylamine. Studies 4 and 5 will evaluate the efficacy of nicotine/mecamylamine treatment for smoking cessation among heavy drinkers, and will also determine whether ad lib alcohol consumption is suppressed by this treatment. In a randomized, double-blind trial, subjects will receive eight weeks of treatment using either combined nicotine/mecamylamine administration, nicotine alone, mecamylamine alone or placebo. Alcohol consumption and relapse to smoking will be assessed during treatment and at a six-month follow-up. Study 6 will evaluate the efficacy of nicotine/mecamylamine treatment in patients undergoing treatment for alcohol dependence. Smoking behavior as well as relapse to alcohol will be monitored over eight weeks. The results of these studies will contribute to the understanding of factors mediating the reinforcing actions of concurrent alcohol/nicotine use and will extend the generality of effective smoking cessation treatments to individuals exhibiting excessive alcohol use or dependence. In addition, this research may lead to the development of nicotinic treatments that reduce alcohol consumption among heavy drinkers and promote abstinence from alcohol in alcoholics.